Patent GB-782971-A (GB)
Title: Basically substituted carboxylic acid amides and a process for making them
IPC: C07C237/00
Filed: 1953-08-18
Abstract: The invention comprises compounds of the formula <FORM:0782971/IV (a)/1> in which R1 represents an alkyl radical having at most 4 carbon atoms, R2 represents an alkylene radical having at most 4 carbon atoms, R3 represents an alkyl or alkenyl radical having at most 5 carbon atoms, and salts of these compounds.  Such compounds are obtained by acylating the corresponding substituted aniline with an aliphatic amino-carboxylic acid of the formula HOOC-R2.NHR3 or a functional derivative thereof such as a halide, ester, anhydride, amide or azide, or by acylating the corresponding substituted aniline with a halogen carboxylic acid of the formula HOOC-R2-Hal or a functional derivative thereof such as a halide, ester, anhydride, amide or azide, and then condensing the halogeno-acylamide so obtained with a primary amine of the formula R3NH2.  Substituted anilines specified are 1-amino-2-methyl-6-chlorobenzene, 1-amino-2-butyl-6-chlorobenzene, 1-amino-2-methyl-6-bromobenzene, 1 - amino - 2 - propyl - 6 - bromobenzene, 1 - amino - 2 - isopropyl - 6 - chlorobenzene and 1 - amino - 2 - ethyl - 6 - chlorobenzene.  As aliphatic aminocarboxylic acids there may be used methyl-, ethyl-, isopropyl- and n-butyl-aminoacetic acids, and ethyl-, butyl- and isopropyl-aminopropionic acids.  As halogen-carboxylic acids there are specified chloracetic, a - and b -chloropropionic and a -chlorobutyric acid and the corresponding bromo and iodo compounds (advantageously employed as a halide, amide, ester, anhydride or azide).  As primary amines of the formula R3NH2 there may be used methylamine, ethylamine, propylamine and butylamine.  The products may be converted to salts with acids such as acetic, lactic, aminosulphonic, phosphoric, hydrochloric or hydrobromic acid.  In examples: (1) (a) 1 - amino - 2 - methyl - 6 - chlorobenzene and chloroacetyl chloride are reacted in benzene in the presence of sodium acetate to give 1-(chloracetylamino) - 2 - methyl - 6 - chlorobenzene; (1 (b)) the product of Example 1 (a) is reacted with ethylamine in ethanol to give 1-(ethylamino - acetylamino) - 2 - methyl - 6 - chlorobenzene and its hydrochloride; (2) the product from Example 1 (a) is reacted with n-butylamine to give 1-(butylamino-acetylamino)-2-methyl-6-chlorobenzene (as hydrochloride) from which the free base and the corresponding phosphate are prepared; (3), (4) and (5) the product of Example 1 (a) is reacted with n-propylamine, allylamine and isobutylamine respectively; (6) 1-(a -bromopropionylamino)-2-methyl - 6 - chlorobenzene (from the reaction of 1 - amino - 2 - methyl - 6 - chlorobenzene with a -bromopropionyl chloride) is reacted with butylamine to give 1-(a -butylamino-propionylamino) - 2 - methyl - 6 - chlorobenzene; (7) 1 - (b  - chloropropionylamino) - 2 - methyl - 6 - chlorobenzene (from the reaction of 1-amino-2-methyl-6-chlorobenzine and b -chloropropionyl chloride) is reacted with butylamine to form 1-(b  - butylamino - propionylamino) - 2 - methyl - 6 - chlorobenzene; (8) phosphorus oxychloride is run into a mixture of chloracetic acid and 1-amino-2-methyl-6-chlorobenzene.  The separated product, 1-(chloracetylamino)-2-methyl-6-chlorobenzene, is reacted with butylamine to form 1 - (n - butylamino - acetyl - amino) - 2 - methyl - 6 - chloro - benzene; (9) and (11) the same compound is prepared starting from 1 - amino - 2 - methyl - 6 - chlorobenzene and chloracetyl chloride; (10) 1-(b -chloropropionylamino) - 2 - methyl - 6 - chlorobenzene and n-butylamine are reacted; (12) in a similar process to that of (3), the 1-(chloroacetylamino)-2-methyl-6-chlorobenzene is prepared by the reaction of chloracetyl chloride and 1-amino-2-methyl-6-chlorobenzene in the presence of a fatty acid partial ester of a sorbitol polyglycol ether as emulsifier; (13) 1-(chloracetylamino)-2-methyl - 6 - bromo - benzene (from 1 - amino - 2 - methyl - 6 - bromo - benzene and chloracetyl chloride) and n-butylamine are reacted to give 1 - (butylamino - acetylamino) - 2 - methyl - 6 - bromobenzene; (14) n-butylamino-acetic acid chloride (from butylamino-acetic acid and phosphorus pentachloride in acetyl chloride) is reacted with 1-amino-2-methyl-6-chlorobenzene to give 1-o -butylamino-acetylamino-2-methyl-6-chlorobenzene.  Application 22106/98, [Class 81], is referred to.